Vaginal rings are known. Background art in this respect includes the following patent documents.
U.S. Pat. Nos. 3,995,633 and 3,995,634, describe separate, preferably spherical or cylindrical, reservoirs containing different active substances which are assembled in specially constructed holders.
U.S. Pat. No. 4,237,885 describes a tube or coil of polymeric material which is divided into portions by means of a plurality of “spacers” provided in the tube, after which each of the separate tube portions is filled with a different active substance in a silicone fluid and the two ends of the tube are subsequently connected to one another. In this release system, however, transport (diffusion) of active material from one reservoir to the other takes place through the wall of the tube, especially upon prolonged storage, so that the pre-set fixed release ratio between the active substances in question will change over a period of time.
European patent publication 0,050,867 discloses a two-layered vaginal ring which comprises a pharmacologically acceptable supporting ring covered by two layers preferably of silicone elastomers whereby the inner layer is a silicone elastomer loaded with an active substance.
U.S. Pat. No. 4,292,965 describes a ring shaped vaginal delivery system of three layers made of silicone elastomers.
U.S. Pat. No. 4,596,576 describes a two-compartment vaginal ring wherein each compartment contains a different active substance. To achieve a suitable ring with a constant release ratio between the various active substances, the end portions of the compartments are joined by glass stoppers.
Patent Publication WO 97/02015 describes a two-compartments device, a first compartment consisting of a core, a medicated middle layer and a non medicated outer layer, and a second compartment consisting of a medicated core and a non medicated outer layer.
EP 876 815 discloses a vaginal ring (Nuvaring®) which is designed for the simultaneous release of a progestogenic steroid compound and an estrogenic steroid compound in a fixed physiological ratio over a prolonged period of time. The drug delivery system comprises one compartment comprising a thermoplastic polymer core containing the mixture of the progestogenic and estrogenic compounds and a thermoplastic polymer skin, the progestogenic compound being initially dissolved in the polymer core material in a relatively low degree of supersaturation.
From the above disclosures, it is clear that e.g. the material, the layers and the compartments are all aspects of a ring device which play a role in the designs that have been developed.
All choices are usually made with a view to obtain a constant release pattern, which is complicated when two or more active substances are involved. The latter is of particular importance in the field of contraception, as for this purpose often a combination of a progestagen and an estrogen is used. Also in hormone replacement, however, it is desired to have rings which deliver combinations of drugs.
Among the above disclosures, EP 876 815 clearly sets a standard; it involves a one-compartment design, it obviates the need for silastic polymer by using EVA combinations, and it releases two or more active substances in a substantially constant ratio to one another over a prolonged period in time.
As any product of technology at all times however, also the latter can still be improved upon. The drug delivery device disclosed in EP 876815 is physically stable only when stored below room temperature. It requires storage and transport below room temperature which is expensive and requires a lot of attention. Moreover, if not stored below room temperature, steroid eventually crystallizes out onto the skin of the device which may lead to uncontrollable and high burst release.
The subject improved drug delivery system solves this problem since it is physically stable under room temperature conditions and thus does not need special storage and transportation conditions.
Moreover, in the subject improved drug delivery system, it is possible to adjust the release rate of more than one pharmaceutically active compound independently from one another, while maintaining the physical stability of the system.